AzTrials
AzTrials

CholangitisCOBRANCT05750966

Short-course Antibiotics vs Standard Course Antibiotics in Patients With Cholangitis

A study testing cefrtriaxone, gentamicin, cefuroxim, ciprofloxin or other antibiotics according to local guideline (24 hours) and cefrtriaxone, gentamicin, cefuroxim, ciprofloxin or other antibiotics according to local guideline (4 to 7 days) in people with Cholangitis, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 31 sites in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The goal of this multicentre randomized controlled trial is to investigate if a very short-course of antibiotics (1 day) for cholangitis after adequate drainage is non-inferior with respect to clinical cure in comparison with a standard course of antibiotics (4 to 7 days). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cholangitis
What is being tested?
cefrtriaxone, gentamicin, cefuroxim, ciprofloxin or other antibiotics according to local guideline (24 hours) and cefrtriaxone, gentamicin, cefuroxim, ciprofloxin or other antibiotics according to local guideline (4 to 7 days)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
410 participants
Where
31 sitesNetherlands
Study dates
19 Jul 2023to 1 Jun 2026
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with acute cholangitis due to common bile duct stones, benign or malignant distal biliary obstruction or distal biliary stent dysfunction (only stents in situ for a minimum of 30 days)
  • ERCP with adequate biliary drainage (all common bile duct stones are removed and/or there is adequate flow of clear bile with or without a biliary stent(s))
  • Absence of fever (temperature <38.5°C) or a decrease of body temperature of at least 1°C has occurred within 24 hours after ERCP
  • Age ≥ 18 years
  • Written informed consent (IC)

Who cannot join

  • Other aetiologies of acute cholangitis (e.g. primary sclerosing cholangitis, (sub)hilar and/or intrahepatic strictures or hilar stents)
  • A recurrent cholangitis (within 3 months)
  • Patients with surgically altered anatomy (leading to biliary-enteric anastomosis)
  • Concomitant pancreatitis, according to International Association of Pancreatology/American Pancreatic Association guidelines.[18] Acute pancreatitis is diagnosed in case of fulfilment of 2 out of 3 of the following criteria:
  • Upper abdominal pain
  • Serum amylase or lipase >3x ULN
Show all 20Show fewer
  • Signs of acute pancreatitis on imaging
  • Concomitant cholecystitis, according to TG18 criteria.[19] Acute cholecystitis is suspected in case one item in A is met and one item in B and C.
  • Local signs of inflammation
  • A1: Murphy's sign
  • A2: Right upper quadrant mass/pain/tenderness B. Systemic signs of inflammation
  • B1: Fever
  • B2: Elevated C-reactive protein
  • B3: Elevated WBC count C. Imaging findings characteristic of acute cholecystitis
  • Concomitant liver abscess
  • Another additional infectious diagnosis
  • Admission on an Intensive Care Unit (ICU) at time of randomisation
  • Use of maintenance antimicrobial therapy
  • Use of immunosuppressants
  • Neutropenia

Trial locations and contacts

31 sites in 1 country.

31 sites in 1 country

Netherlands31 sites

  • Jeroen Bosch Ziekenhuis

    's-Hertogenbosch, North Brabant, 5223 GZ

  • Flevoziekenhuis

    Almere Stad, Flevoland, 1315 RA

  • Meander MC

    Amersfoort, Utrecht, 3813 TZ

  • Amstelland Ziekenhuis

    Amstelveen, North Holland, 1186 AM

  • Amsterdam UMC

    Amsterdam, North Holland, 1081 HZ

  • OLVG

    Amsterdam, North Holland, 1091 AC

  • Rijnstate Ziekenhuis

    Arnhem, Gelderland, 6815 AD

  • Reinier de Graaf Gasthuis

    Delft, South Holland, 2625 AD

  • Deventer Ziekenhuis

    Deventer, Overijssel, 7416 SE

  • Albert Schweitzer Ziekenhuis

    Dordrecht, South Holland, 3318 AT

  • Catharina Ziekenhuis

    Eindhoven, North Brabant, 5623 EJ

  • Medisch Spectrum Twente

    Enschede, Overijssel, 7512 KZ

  • Groene Hart Ziekenhuis

    Gouda, South Holland, 2803 HH

  • Universitair Medisch Centrum Groningen

    Groningen, Provincie Groningen, 9713 GZ

  • Martini Ziekenhuis

    Groningen, Provincie Groningen, 9728 NT

  • Spaarne Gasthuis

    Hoofddorp, North Holland, 2134 TM

  • Dijklander Ziekenhuis

    Hoorn, North Holland, 1624 AR

  • Medisch Centrum Leeuwarden

    Leeuwarden, Provincie Friesland, 8934 AD

  • Leids Universitair Medisch Centrum

    Leiden, South Holland, 2333 ZA

  • Alrijne Ziekenhuis

    Leiderdorp, South Holland, 2353 GA

  • Maastricht UMC+

    Maastricht, Limburg, 6229 HX

  • St. Antonius Ziekenhuis

    Nieuwegein, Utrecht, 3435 CM

  • Radboud umc

    Nijmegen, Gelderland, 6525 GA

  • Canisius Wilhelmina Ziekenhuis

    Nijmegen, Gelderland, 6532 SZ

  • Erasmus MC

    Rotterdam, South Holland, 3015 GD

  • Maasstad Ziekenhuis

    Rotterdam, South Holland, 3079 DZ

  • Haaglanden Medisch Centrum

    The Hague, South Holland, 2512 VA

  • Elisabeth Tweesteden Ziekenhuis

    Tilburg, North Brabant, 5022 GC

  • Universitair Medisch Centrum Utrecht

    Utrecht, Utrecht, 3584 CX

  • Zaans Medisch Centrum

    Zaandam, North Holland, 1502 DV

  • Isala

    Zwolle, Overijssel, 8025 AB

Other trials in Netherlands

About this study

Official title: Very Short-course Versus Standard Course Antibiotic Therapy in Patients With Acute ChOlangitis After Adequate Endoscopic BiliaRy drAinage

The goal of this multicentre randomized controlled trial is to investigate if a very short-course of antibiotics (1 day) for cholangitis after adequate drainage is non-inferior with respect to clinical cure in comparison with a standard course of antibiotics (4 to 7 days). Secondary objectives include:

  • Will a one-day course of antibiotics for cholangitis after adequate drainage be non-inferior with respect to relapse of cholangitis and mortality in comparison with a standard course of antibiotics?
  • Will a one-day course of antibiotics for cholangitis after adequate drainage result in less adverse drug events in comparison with a standard course of antibiotics?
  • Will a one-day course of antibiotics for cholangitis after adequate drainage reduce length of hospital stay?
  • Will a one-day course of antibiotics for cholangitis after adequate drainage improve quality of life?
  • Will a one-day course of antibiotics for cholangitis after adequate drainage be cost-effective?
Read the detailed description

Acute cholangitis is an infection of the biliary tract which is managed with biliary drainage and antibiotic therapy (ABT). Currently the international Tokyo Guidelines 2018 (TG18) recommend 4 to 7 days of ABT after source control. The national SWAB guideline of 2020 suggests a course of one to 3 days after biliary drainage. There are no randomized studies to guide the duration of ABT for acute cholangitis. Our recent retrospective study in the Netherlands showed that a short course of ABT seems safe and more evidence is available showing that other bacterial infections, including abdominal and bloodstream infections, can be treated with a short antibiotic course than previously assumed. Hence, the hypothesis is that a very short-course of ABT for acute cholangitis is non-inferior to a course of 4 to 7 days after adequate biliary drainage.

This study is designed as a multicenter non-inferiority randomized controlled trial. Patients will be randomly assigned to the intervention group (one day of antibiotic therapy after ERCP) or the comparator group (4 to 7 days of antibiotic therapy after ERCP).

Conditions
Cholangitis
Being tested
cefrtriaxone, gentamicin, cefuroxim, ciprofloxin or other antibiotics according to local guideline (24 hours), cefrtriaxone, gentamicin, cefuroxim, ciprofloxin or other antibiotics according to local guideline (4 to 7 days)
Keywords
antibiotics, randomized controlled trial
Medical subject headings
Cholangitis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • cefrtriaxone, gentamicin, cefuroxim, ciprofloxin or other antibiotics according to local guideline (24 hours)Drug

    Also called ceftriaxone, gentamicin, cefuroxim, ciprofloxacin

    The duration of antibiotics is 24 hours after adequate biliary drainage. The choice of antibiotics will be according to local protocol and/or national Dutch SWAB guidelines. The most common antibiotics are described above, but this can differ based on allergies, local protocol or previous cultures. Drug classes may include: aminoglycosides, carbapenems, cefalosporins, fluorquinolones, sulfonamides, penicillines.

  • cefrtriaxone, gentamicin, cefuroxim, ciprofloxin or other antibiotics according to local guideline (4 to 7 days)Drug

    Also called ceftriaxone, gentamicin, cefuroxim, ciprofloxacin

    The duration of antibiotics is 4 to 7 days after adequate biliary drainage. The choice of antibiotics will be according to local protocol and/or national Dutch SWAB guidelines. The most common antibiotics are described above, but this can differ based on allergies, local protocol or previous cultures. Drug classes may include: aminoglycosides, carbapenems, cefalosporins, fluorquinolones, sulfonamides, penicillines.

Study groups in NCT05750966
Study groupRoleWhat they receive
Very short-course antibioticsExperimentalThe antibiotic regimens will be according to the local hospital's antibiotic guideline for cholangitis (e.g. dosage form, dosage, frequency)and/or the national SWAB guideline in the Netherlands. In the experimental group, duration of ABT after adequate drainage will be 1 day. The duration will be 4 days and can be extended to 7 days in case of gram-negative bacteraemia, according to the national SWAB guideline regarding gram-negative sepsis.
Receives: Drug: cefrtriaxone, gentamicin, cefuroxim, ciprofloxin or other antibiotics according to local guideline (24 hours)
Standard course antibioticsActive comparatorThe antibiotic regimens will be according to the local hospital's antibiotic guideline for cholangitis, which are based on the previously mentioned national SWAB guideline. This means that the type of ABT, dosage and frequency will be comparable to the experimental group. In the comparator group treatment duration with ABT after ERCP will be according to the international well known and widely used TG18. The duration will be 4 days and can be extended to 7 days in case of gram-negative bacteraemia, according to the national SWAB guideline regarding gram-negative sepsis.
Receives: Drug: cefrtriaxone, gentamicin, cefuroxim, ciprofloxin or other antibiotics according to local guideline (4 to 7 days)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. clinical cure rate by day 14 after ERCP without relapse by day 30

    Clinical cure is defined as the absence of both fever (>38°C) and/or shaking chills, and initial presenting symptoms. Relapse is defined as the initiation of new antibiotic therapy for recurrent cholangitis, subsequent infection in the hepatic-pancreatic-biliary region, or any other subsequent infection possibly related to the initial episode of cholangitis.

    Measured: 30 days

Secondary outcomes (8)

  1. All-cause 90-day mortality.

    Mortality, which includes all causes.

    Measured: 90 days

  2. Relapse of cholangitis within 90 days

    Relapse is defined as the initiation of new antibiotic therapy for recurrent cholangitis, subsequent infection in the hepatic-pancreatic-biliary region, or any other subsequent infection possibly related to the initial episode of cholangitis.

    Measured: 90 days

  3. Rate of any other subsequent infection requiring antibiotic therapy within 90 days.

    Subsequent infections excluding recurrent cholangitis.

    Measured: 90 days

  4. Rate of subsequent infections with MDR bacteria or Clostridioides difficile within 90 days.

    Subsequent infections, in particular due to resistant bacteria.

    Measured: 90 days

  5. Rate of other adverse drug events within 14 days

    Includes: rash, diarrhoea (defined as ≥3 x loose stools per day), liver function abnormalities (defined as ≥5 x upper limit of normal (ULN) elevation in alanine aminotransferase (ALT) or ≥2 x ULN elevation in alkaline phosphatase (ALP) or ≥3 x ULN elevation in ALT and simultaneous elevation of total bilirubin concentration exceeding 2 x ULN (according to European association for the Study of the Liver Clinical Practice Guidelines: Drug-induced liver injury) AND without evidence of persistent obstruction on imaging OR elevation of liver enzymes after initial decrease. Lastly, other adverse drug events includes acute kidney injury, defined as increase in serum creatinine by ≥26.5 micromol/L within 48 hours or increase in serum creatinine to ≥1.5 times baseline (according to Kidney Disease: Improving Global Outcomes guidelines).

    Measured: 14 days

  6. Length of intensive care and hospital stay for the initial episode of cholangitis.

    Length of IC and hospital stay defined in days.

    Measured: 30 days

  7. Quality of life and health utility.

    This will be evaluated using the RAND-36 and EQ-5D-5L at day 7, day 30 and day 90.

    Scale title (RAND-36): Research and Devevelopment-36 Minimum raw score: 45 Maximum raw score : 198 Higher scores mean a better outcome.

    Scale title (EQ-5D-5L): European Quality of Life-5 Dimensions-5 Levels score Minimum score: 11111 Maximum score: 55555 Higher scores mean a worse outcome.

    Measured: 90 days

  8. Societal costs and cost-effectiveness/-utility

    The costs per cured patient without relapse and the costs per quality adjusted life year (QALY) Scale Title: Quality Adjusted Life Year. One quality-adjusted life year (QALY) is equal to 1 year of life in perfect health.QALYs are calculated by estimating the years of life remaining for a patient following a particular treatment or intervention and weighting each year with a quality-of-life score (on a 0 to 1 scale).

    Minimum score: 0 Maximum score: 1 Higher scores mean a better outcome.

    Measured: 90 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Mar 2023
  2. Study start19 Jul 2023
  3. Primary completion1 Apr 2026
  4. Study completion1 Jun 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
This study is designed as an open-label multicenter non-inferiority RCT. Patients will be randomly assigned to the intervention group (one day of ABT after ERCP) or the comparator group (4 to 7 days of ABT after ERCP).
Masking
None (open label)
Enrolment
410 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05750966
Sponsor's protocol ID
2022.0292
Other IDs
2022-002624-12, NL80410.029.22
Acronym
COBRA
Status last verified
Jun 2026
First submitted
3 Feb 2023
Last updated
11 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Miura F, Okamoto K, Takada T, Strasberg SM, Asbun HJ, Pitt HA, Gomi H, Solomkin JS, Schlossberg D, Han HS, Kim MH, Hwang TL, Chen MF, Huang WS, Kiriyama S, Itoi T, Garden OJ, Liau KH, Horiguchi A, Liu KH, Su CH, Gouma DJ, Belli G, Dervenis C, Jagannath P, Chan ACW, Lau WY, Endo I, Suzuki K, Yoon YS, de Santibanes E, Gimenez ME, Jonas E, Singh H, Honda G, Asai K, Mori Y, Wada K, Higuchi R, Watanabe M, Rikiyama T, Sata N, Kano N, Umezawa A, Mukai S, Tokumura H, Hata J, Kozaka K, Iwashita Y, Hibi T, Yokoe M, Kimura T, Kitano S, Inomata M, Hirata K, Sumiyama Y, Inui K, Yamamoto M. Tokyo Guidelines 2018: initial management of acute biliary infection and flowchart for acute cholangitis. J Hepatobiliary Pancreat Sci. 2018 Jan;25(1):31-40. doi: 10.1002/jhbp.509. Epub 2018 Jan 8.

    PubMed 28941329

  • Sieswerda E, Bax HI, Hoogerwerf JJ, de Boer MGJ, Boermeester M, Bonten MJM, Dekker D, van Wijk RG, Juffermans NP, Kuindersma M, van der Linden PD, Melles DC, Pickkers P, Schouten JA, Rebel JR, van Zanten ARH, Prins JM, Wiersinga WJ. The 2021 Dutch Working Party on Antibiotic Policy (SWAB) guidelines for empirical antibacterial therapy of sepsis in adults. BMC Infect Dis. 2022 Aug 11;22(1):687. doi: 10.1186/s12879-022-07653-3.

    PubMed 35953772

  • Haal S, Wielenga MCB, Fockens P, Leseman CA, Ponsioen CY, van Soest EJ, van Wanrooij RLJ, Sieswerda E, Voermans RP. Antibiotic Therapy of 3 Days May Be Sufficient After Biliary Drainage for Acute Cholangitis: A Systematic Review. Dig Dis Sci. 2021 Dec;66(12):4128-4139. doi: 10.1007/s10620-020-06820-3. Epub 2021 Jan 19.

    PubMed 33462749

  • Overdevest AG, Sieswerda E, Haal S, Bogaards JA, Baven-Pronk MAMC, Bogte A, Boparai KS, Ter Borg F, Brink MA, van Delft F, Dik VK, Fockens P, Gilissen LPL, Hadithi M, Hazen WL, van der Heide F, den Hollander WJ, Inderson A, de Jonge PJF, Kuiken SD, Munneke JM, Perk LE, Poen AC, Poley JW, Quispel R, Scheffer RCH, Scholvinck DW, van Soest EJ, Tan ACITL, Thijs WJ, Venneman NG, Verdonk RC, van de Vrie W, Vrolijk JM, van Wanrooij RLJ, Weijenborg PW, Dijkgraaf MGW, Prins JM, Voermans RP. Antibiotic treatment for 1 day versus 4-7 days in patients with acute cholangitis after adequate endoscopic biliary drainage (COBRA): study protocol for a randomized controlled trial. Trials. 2026 Feb 14;27(1):222. doi: 10.1186/s13063-026-09524-7.

    PubMed 41689066

Questions about this trial

What is this clinical trial studying?

A study testing cefrtriaxone, gentamicin, cefuroxim, ciprofloxin or other antibiotics according to local guideline (24 hours) and cefrtriaxone, gentamicin, cefuroxim, ciprofloxin or other antibiotics according to local guideline (4 to 7 days) in people with Cholangitis, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 31 sites in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

clinical cure rate by day 14 after ERCP without relapse by day 30 (time frame: 30 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05750966, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in